Method and a device for determining the hydration and/or nutrition status of a patient

ABSTRACT

The invention relates to the field of monitoring the hydration and/or nutrition status of a patient. According to the invention a method is provided to determine at least one of a mal-hydration component, an adipose tissue component and a lean tissue component of a patient comprising the steps of determining chemical or physical properties of the patient and deriving the at least one component on the basis of the determined chemical or physical properties of the patient and previously determined values of a mass or volume fraction of water in lean tissue and a mass or volume fraction of water in adipose tissue. The invention also relates to a device for carrying out the method according to the invention and to a computer program product to be used on such a device.

This application is a continuation of application Ser. No. 11/630,965,filed Dec. 28, 2006, which is a nationalization of PCT/EP2004/014544filed Dec. 21, 2004 and published in English, which claims priority fromPCT/EP2004/07023, filed Jun. 29, 2004.

The invention relates to the field of monitoring the hydration and/ornutrition status of a patient.

The kidneys carry out several functions for maintaining the health of ahuman body. First, they control the fluid balance by separating anyexcess fluid from the patient blood volume. Second, they serve to purifythe blood from any waste substances like urea or creatinine. Last notleast they also control the levels of certain substances in the bloodlike electrolytes in order to ensure a healthy and necessaryconcentration level.

In case of renal failure ingested fluid accumulates in body tissues andthe vascular system causing increased stress on the circulatory system.This surplus fluid has to be removed during a dialysis treatment byultrafiltration of the blood. If insufficient fluid is removed the longterm consequences can be severe, leading to high blood pressure andcardiac failure. Cardiac failure itself is many times more likely tooccur in dialysis patients and it is thought that states of fluidoverload are one of the major contributing factors. Removal of too muchfluid is also dangerous since the dialysis patient becomes dehydratedand this invariably leads to hypotension.

The dry weight (for the sake of simplicity the words “weight” and “mass”shall be used synonymously throughout this patent applicationdocument—which also is usual practise in the medical field) defines theweight of a patient that would be achieved if the kidneys were workingnormally. In other words this represents the optimal target weight (orfluid status) which should be achieved in order to minimisecardiovascular risk. Dry weight has always been an elusive problem inroutine clinical practise due to lack of quantitative methods for itsassessment. Currently the dry weight problem is approached usingindirect indicators like e.g. blood pressure, echocardiographicinvestigations and subjective information such as X-rays. Furthermore ithas been particularly difficult to define a set of conditions which areuniversally accepted as the dry weight standard.

A promising method to derive the fluid status of a patient involves theuse of bioimpedance measurements. A small alternating current is appliedto two or more electrodes which are attached to a patient and thecorresponding electric potential difference is measured. The variousfluid compartments of a human body contribute differently to themeasured signals. The use of multiple frequencies allows the water inthe intracellular volume (ICV) and the extracellular volume (ECV) to bedetermined. An example of such a device is described in theinternational patent application WO 92/19153. However, this documentdiscloses no method regarding how the dry weight of the particularpatient can be derived.

U.S. Pat. No. 5,449,000 describes a bioimpedance system also usingmultiple frequencies to determine water mass in the ECV and ICV.Furthermore certain population dependent data are taken for using andchoosing so-called population prediction formulas. The body compositionis then analysed by using these formulas and with the help of segmentalbioimpedance signals.

The international patent application WO 02/36004 A1 describes a methodand a device for deriving the dry weight of a patient with renal failureusing a bioimpedance device by extrapolating an excess water volume inthe extracellular volume to a condition where there would be no renalfailure. By a similar procedure a mass correction term accounting fordeviations within healthy human beings and being attributed to certaintissues can be derived.

The international patent application WO 03/053239 A1 discloses acompartmental model which addresses the variation in healthy humanbeings in certain body compartments in order to better separate amal-hydration volume and other tissue components in particular with theaid of bioimpedance measurements. With such a device information on thenutrition status of a patient can also be obtained.

U.S. Pat. No. 6,615,077 describes an approach for monitoring a dialysistreatment by a bioimpedance device in order to correlate the signalswith the progress of the treatment.

In view of the prior art there is a need for a simple method thatrequires only very few fundamental parameters and that nonethelessprovides reliable results on the hydration, nutrition and trainingstatus of a patient at the same time. It is an object of this inventionto provide such a method.

The problem of the invention is solved by a method according to claim 1,i.e. by a method to determine at least one of a mal-hydration component,an adipose tissue component and a lean tissue component of a patientcomprising the steps of determining chemical or physical properties ofthe patient and deriving the at least one component on the basis of thedetermined chemical or physical properties of the patient and previouslydetermined values of a mass or volume fraction of water in lean tissueand a mass or volume fraction of water in adipose tissue.

The invention is based on the observation that a model dividing the bodyof a patient into a lean tissue compartment, an adipose tissuecompartment and a mal-hydration compartment is already adequate tominimise the number of parameters involved and to still provide reliableresults. The inventors further recognised that it is sufficient toestablish values for a water volume or mass fraction for the lean tissueon one hand and for the adipose tissue on the other hand. To apply themodel these fractions can be taken as fixed values independent of thepatient the method is applied to. According to the concept of theinvention it is, apart from the mal-hydration water compartment, mainlythe individual mixture of these two types of tissues that contributes tothe differential water distribution within the patient so that it issufficient to explicitly consider these two types of tissues for thisaspect.

In the framework of the invention adipose tissue is considered toconsist of fat cells or adipocytes suspended in extracellular fluid. Theadipocytes themselves consist predominantly of lipids or fat and a smallquantity of intracellular fluid. Adipose tissue should therefore not beconfused with fat even though they are related. Fat is simply the purelipid whilst adipose tissue is a mixture of fat and water. Theadipocytes bind a proportion of extracellular fluid which makes up thetotal adipose tissue mass. This extracellular fluid is therefore notfree fluid and must be taken into account when calculating a patient'sexcess fluid.

In the prior art two-compartment models have been known that divide thehuman body into a fat-free mass and a fat mass compartment (e.g.: K. J.Ellis, “Human Body Composition: In Vivo Methods”, Physiological Reviews80, 649 (2000)). In such a model the fat mass compartment only consistsof fat or lipids whereas the remainder of the body, including the water,is lumped together in the fat-free mass compartment. This is differentto the present invention that distinguishes between adiposetissue—including a non-vanishing water component—on one hand and leantissue on the other hand. Though the lean tissue compartment is—apartfrom the mal-hydration compartment—again defined as the “remainder” ofthe body mass, the two tissues are further distinguished by theirdifferent water fractions.

It is also an object of the invention to provide a device for anon-invasive, accurate and easy to use body compartment assessment. Theinvention therefore also concerns a device according to claim 9 forcarrying out the method according to the invention, i.e. a devicecomprising a measurement and/or input unit configured to provide valuesfor chemical or physical properties of the patient to be determined, anevaluation unit configured to derive at least one component of amal-hydration component, an adipose tissue component and a lean tissuecomponent on the basis of the determined chemical or physical propertiesof the patient and previously determined values of a mass or volumefraction of water in lean tissue and a mass or volume fraction of waterin adipose tissue, and a communication link between the measurementand/or input unit and the evaluation unit.

In a preferred embodiment the evaluation unit is also configured tocontrol the measurement and/or input unit for determining at least oneof the chemical or physical properties of the patient.

In a further preferred embodiment the evaluation unit is amicroprocessor unit which in turn comprises a microprocessor programstorage unit, wherein in the microprocessor program storage unit aprogram for deriving the at least one component on the basis of thedetermined chemical or physical properties of the patient and previouslydetermined values of a mass or volume fraction of water in lean tissueand a mass or volume fraction of water in adipose tissue is stored.

A computer program product according to claim 18 which comprises astorage medium on which a computer program is stored which is to bestored in a device according to the invention for carrying out themethod according to the invention where the evaluation unit comprises amicroprocessor storage unit, is also constituting a part of theinvention.

Various further embodiments of the invention are subject of thesubclaims of the independent claims.

For an improved understanding of the invention, non-restrictive exampleswill be described with reference to the appended drawings in which

FIG. 1 a shows a schematic illustration of the three components of thebody of a patient representing the mal-hydration mass M_(EX), the leantissue mass M_(LT) and the adipose tissue mass M_(AT),

FIG. 1 b shows a schematic illustration of the three components of abody of a patient according to FIG. 1 a (right hand side) in relation tothe mass components as derived by dual x-ray absorptiometry (DXA) (lefthand side),

FIG. 2 shows a compilation of example values for the various parametersrequired in the example embodiments of the invention for the calculationof the body mass components,

FIG. 3 schematically shows an embodiment of a device for the assessmentof the body composition of a patient according to the present invention,and

FIG. 4 shows a bioimpedance electrode arrangement for whole bodybioimpedance measurements (left hand side) and a bioimpedance electrodearrangement for segmental body bioimpedance measurements (right handside).

As illustrated in FIG. 1 a the body of a patient can be divided intothree components: an excess fluid or mal-hydration component with massM_(EX), a lean tissue component with mass M_(LT) and an adipose tissuecomponent with mass M_(AT). For all three components the extracellularwater (ECW) and intracellular water (ICW) together with othercontributions (minerals, proteins, lipids etc.) are also shown in FIG. 1a. The excess fluid M_(EX) which mainly accumulates in the ECV space isan indicator of the mal-hydration status of a patient. In a healthysubject M_(EX) would be vanishing. M_(EX) may also have a negative valueindicating a hydration status where the patient is over hydrated.

The lean and the adipose tissue are distinguished in the framework ofthis application by their water contents. The lean tissue mass M_(LT)comprises bones, organs (including blood) and muscles, but no lipids.More sophisticated models could be considered to include the influenceof bone or other tissues, but for the present purpose such refinementsare neglected. Adipose tissue mass M_(AT), on the other hand, is assumedto be largely comprised of lipids and water in the form of fat cells oradipocytes.

According to the concept of the invention it is necessary to distinguishbetween the mass fraction Λ_(LT) of water in lean tissue as a firsttissue and the corresponding mass fraction Λ_(AT) of water in adiposetissue as a second tissue:

$\begin{matrix}{{\Lambda_{LT} \equiv \frac{D \cdot \left( {{ECW}_{LT} + {ICW}_{LT}} \right)}{M_{LT}}},} & (1) \\{{\Lambda_{AT} \equiv \frac{D \cdot \left( {{ECW}_{AT} + {ICW}_{AT}} \right)}{M_{AT}}},} & (2)\end{matrix}$

wherein D is the density of water (D=0.99823 kg/litre at 36° C.; for thepresent purpose a single density value is considered to be sufficient,however small variations due to solutes in the different watercompartments may be introduced), ECW_(LT) and ICW_(LT) are the volumesof extracellular and intracellular water in the lean tissue, the latterhaving the total mass M_(LT), and ECW_(AT) and ICW_(AT) are the volumesof extracellular and intracellular water in the adipose tissue, thelatter having the total mass M_(AT). Eqs. (1) and (2) may of course alsobe written in terms of fractions per tissue volume, as volume per massor as mass per volume without leaving the concept of the invention. Itis only important that the water contribution to the lean tissue on onehand and to the adipose tissue on the other hand is considereddifferently.

The fractions Λ_(LT) and Λ_(AT) each have a contribution Λ_(ECW) fromthe extracellular water and a contribution Λ_(ICW) from theintracellular water:

$\begin{matrix}{{\Lambda_{{ECW},{LT}} \equiv \frac{D \cdot {ECW}_{LT}}{M_{LT}}},} & (3) \\{{\Lambda_{{ICW},{LT}} \equiv \frac{D \cdot {ICW}_{LT}}{M_{LT}}},} & (4) \\{{\Lambda_{{E\; {CW}},{AT}} \equiv \frac{D \cdot {ECW}_{AT}}{M_{AT}}},} & (5) \\{\Lambda_{{I\; {CW}},{AT}} \equiv {\frac{D \cdot {ICW}_{AT}}{M_{AT}}.}} & (6)\end{matrix}$

According to the concept of the present invention it is sufficient topreviously determine at least values for the mass fractions Λ_(LT) andΛ_(AT). In more refined embodiments of the invention the mass fractionsas defined by some or all the Eqs. (3) to (6) are used. To determinesuch values various experimental methods may be employed. Once thesevalues are established, as will be shown below, a set of rather simpleequations may be used for routine application that can also be employedtogether with less sophisticated experimental methods but still lead toaccurate and reliable results for the masses of the three bodycomponents M_(EX), M_(LT) and M_(AT).

Using dual x-ray absorptiometry (DXA) or dilution experiments asreference data it is possible to derive the mass fractions ofextracellular and intracellular water independently for the lean tissueand the adipose tissue mass components. A good review of such and othermethods is given in the aforementioned article from K. J. Ellis.

In DXA the attenuation of two x-ray photons having different photonenergies is compared. As a result it is possible to distinguish betweenfat mass M_(LIPID), lean tissue mass M_(LT,DXA) according to DXA and thetotal bone mineral content mass M_(TBMC) of a patient. The relation ofthese mass components to the components as used by the invention isshown in FIG. 1 b. It is important to note that the fat mass M_(LIPID)does only represent the adipose lipids of the adipose tissue, but notthe adipose water. Furthermore, the lean tissue mass M_(LT) comprisesparts of the lean tissue mass M_(LT,DXA) according to DXA and the totalbone mineral content mass M_(TBMC). The lean tissue mass M_(LT,DXA)according to DXA, on the other hand, also comprises the mal-hydrationmass M_(EX) and the adipose water mass.

With the help of dilution experiments as a further reference methodcertain compartments of a body can be probed by selecting appropriatetracer substances that dilute just in the chosen compartment. Typicalexamples are the ECW, ICW or the total body water (TBW) volumes.

Taking the reference data from such experiments the mass fractions ofEqs. (1) to (6) can be derived by optimisation and also by analyticalmethods in an effort to map the observed data as closely as possible foras many individuals as possible. An example result of such a procedureis compiled in FIG. 2.

Once at least one of the water mass fractions Λ_(LT), Λ_(ECW,LT) orΛ_(ICW,LT) of the lean tissue mass component and at least one of thewater mass fractions Λ_(AT), Λ_(ECW,AT) or Λ_(ICW,AT) of the adiposetissue mass component have been previously determined it is now possibleto derive vice versa at least one of the masses of the mal-hydrationmass M_(EX), the lean tissue mass M_(LT) and the adipose tissue massM_(AT) from routine experimental measurement data of chemical orphysical properties of the patient without having to use all theexperimental methods that were applied to obtain the reference data.Depending on the kind of chemical or physical properties that are to bedetermined by the routine measurements, various modes of the inventionare possible. Before an exemplary device according to the invention willbe explained in detail five examples for such methods according to theinvention are described:

EXAMPLE 1

Chemical or physical properties of the patient to be determined:

ECW: volume of the total extracellular water of the patient,ICW: volume of the total intracellular water of the patient,M: whole body mass of the patient.

Each of these properties can be split into contributions from the threecomponents:

ECW=ECW _(EX) +ECW _(LT) +ECW _(AT)  (7),

ICW=ICW _(LT) +ICW _(AT)  (8),

M=M _(LT) +M _(AT) +M _(EX)  (9).

Using Eqs. (3) to (6), Eqs. (7) to (9) can be solved for the masses ofall three components:

$\begin{matrix}{{M_{EX} = \frac{{D \cdot {ECW}} - {M \cdot \left( {\Lambda_{{ECW},{AT}}k_{1}\Lambda_{{ICW},{AT}}} \right)} + {k_{1}{D \cdot {ICW}}}}{\left( {1 - \Lambda_{{ECW},{AT}} - {k_{1}\Lambda_{{ICW},{AT}}}} \right)}}{wherein}} & (10) \\{{k_{1} = \frac{\Lambda_{{ECW},{AT}} - \Lambda_{{ECW},{LT}}}{\Lambda_{{ICW},{LT}} - \Lambda_{{ICW},{AT}}}},} & (11) \\{{M_{LT} = \frac{{D \cdot {ICW}} - {\left( {M - M_{EX}} \right) \cdot \Lambda_{{ICW},{AT}}}}{\left( {\Lambda_{{ICW},{LT}} - \Lambda_{{ICW},{AT}}} \right)}}{and}} & (12) \\{M_{AT} = {M - M_{LT} - {M_{EX}.}}} & (13)\end{matrix}$

EXAMPLE 2

Chemical or physical properties of the patient to be determined:

TBW: volume of the total body water of the patientM_(TBMC): mass of total bone mineral content of the patientM: whole body mass of the patient.

The total body water TBW can be split into three parts originating fromthe three components:

$\begin{matrix}{{TBW} = {\frac{1}{D}{\left( {{\Lambda_{LT} \cdot M_{LT}} + {\Lambda_{AT} \cdot M_{AT}} + M_{EX}} \right).}}} & (14)\end{matrix}$

The lean tissue mass M_(LT) is split in this example into its waterfraction and a rest fraction M_(Min+Pro) mainly attributing for mineralsand proteins:

M _(LT)=Λ_(LT) ·M _(LT) +M _(Min+Pro)  (15).

Taking k_(TBMC) to be the share of the total bone mineral content massM_(TBMC) of M_(Min+Pro) one has:

M _(TBMC) =k _(TBMC) ·M _(Min+Pro)  (16)

wherein a typical value of k_(TBMC) is 0.2074. Together with the massbalance Eq. (9) the set of Eqs. (14) to (16) can be solved for the threecomponent masses:

$\begin{matrix}{M_{EX} = \frac{{D \cdot {TBW}} - {\frac{M_{TBMC}}{k_{TBMC}\left( {1 - \Lambda_{AT}} \right)}\left( {\Lambda_{LT} - \Lambda_{AT}} \right)} - {\Lambda_{AT} \cdot M}}{\left( {1 - \Lambda_{AT}} \right)}} & (17) \\{M_{LT} = \frac{M_{TBMC}}{k_{TBMC}\left( {1 - \Lambda_{LT}} \right)}} & (18)\end{matrix}$

and M_(AT) is obtained by using Eq. (13).

EXAMPLE 3

Chemical or physical properties of the patient to be determined:

TBW: volume of the total body water of the patientM_(LIPID): lipid mass of the patientM: whole body mass of the patient.

The mass of mal-hydration water can be expressed as

M _(EX) =D(TBW−TW _(LT) −TW _(AT))  (19),

wherein TW_(LT) is the sum of the extra- and intracellular water volumesin the lean tissue and TW_(AT) is the sum of the extra- andintracellular water volumes in the adipose tissue. The lipid massM_(LIPID) of the patient is the mass M_(AT) of the adipose tissuewithout the water mass in the adipose tissue:

M _(LIPID) =M _(AT) −D·TW _(AT) =M _(AT)(1−Λ_(AT))  (20).

Inserting Eqs. (13) and (20) in Eq. (19) by making use of Eqs. (1) and(2) and solving for the mal-hydration water mass M_(EX) one obtains:

$\begin{matrix}{M_{EX} = \frac{{D \cdot {TBW}} - {\Lambda_{LT}M} + {\frac{M_{LIPID}}{1 - \Lambda_{AT}}\left( {\Lambda_{LT} - \Lambda_{AT}} \right)}}{\left( {1 - \Lambda_{LT}} \right)}} & (21)\end{matrix}$

M_(AT) may be calculated by solving Eq. (20) and M_(LT) by solving Eq.(9):

$\begin{matrix}{{M_{AT} = \frac{M_{LIPID}}{\left( {1 - \Lambda_{AT}} \right)}}{and}} & (22) \\{M_{LT} = {M - M_{AT} - {M_{EX}.}}} & (23)\end{matrix}$

EXAMPLE 4

Chemical or physical properties of the patient to be determined:

ECW: volume of the total extracellular water of the patientM_(LIPID): lipid mass of the patientM: whole body mass of the patient.

The mass of mal-hydration water can be expressed as

M _(EX) =D(ECW−ECW _(LT) −ECW _(AT))  (24),

wherein the parameters are as defined in Example 1. Inserting Eqs. (13)and (22) in Eq. (24) by making use of Eqs. (2), (3) and (5) and solvingfor the mal-hydration water mass M_(EX) one obtains:

$\begin{matrix}{M_{EX} = \frac{{D \cdot {ECW}} - {\Lambda_{{ECW},{LT}}M} + {\frac{M_{LIPID}}{1 - \Lambda_{AT}}\left( {\Lambda_{{ECW},{LT}} - \Lambda_{{ECW},{AT}}} \right)}}{\left( {1 - \Lambda_{{ECW},{LT}}} \right)}} & (25)\end{matrix}$

M_(AT) and M_(LT) may be derived similar as in Example 3, i.e. accordingto Eqs. (22) and (23).

EXAMPLE 5

Chemical or physical properties of the patient to be determined:

ECW: volume of the total extracellular water of the patientICV: volume of the total intracellular cells of the patientM: whole body mass of the patient.

This example has similarities with Example 1. However, instead of theICW the intracellular volume ICV as a whole, including the volume ofmatter not being water is determined. In this case it is useful tointroduce further constants that are related to the water mass fractionsas defined by Eqs. (3) to (6).

In analogy to the ICW the total ICV can be split into componentsICV_(AT) for the adipose tissue and ICV_(LT) for the lean tissue. Theseare linked to the masses M_(LT) of the lean tissue component and M_(AT)of the adipose tissue component by proportionality constants ζ_(LT) andζ_(AT) (example values as taken from the international patentapplication PCT/EP2004/007023 are ζ_(LT)=0.620 litres/kg andζ_(AT)=0.987 litres/kg):

ICV=ICV _(LT) +ICV _(AT) =M _(LT)·ζ_(LT) +M _(AT)·ζ_(AT)  (26).

Substituting M_(AT) in Eq. (26) with the help of Eq. (9) and solving theresultant equation for M_(LT), Eq. (27) is obtained:

$\begin{matrix}{M_{LT} = {\frac{{ICV} - {\zeta_{AT}\left( {M - M_{EX}} \right)}}{\zeta_{LT} - \zeta_{AT}}.}} & (27)\end{matrix}$

Before the lean tissue mass M_(LT) can be derived, the mal-hydrationmass M_(EX) has to be calculated. The starting point is again theobservation that this component manifests itself entirely in the ECVspace, i.e. the mal-hydration water volume can be derived as ECW_(EX) bysolving Eq. (7).

Using the following definitions for the volume of extracellular waterper unit mass of lean tissue λ_(ECW,LT),

$\begin{matrix}{{\lambda_{{ECW},{LT}} \equiv \frac{{ECW}_{LT}}{M_{LT}}} = \frac{\Lambda_{{ECW},{LT}}}{D}} & (28)\end{matrix}$

and for the volume of extracellular water per unit mass of adiposetissue ζ_(ECW,AT),

$\begin{matrix}{{{\lambda_{{ECW},{AT}} \equiv \frac{{ECW}_{AT}}{M_{AT}}} = \frac{\Lambda_{{ECW},{AT}}}{D}},} & (29)\end{matrix}$

and further introducing the definition

$\begin{matrix}{{A \equiv \frac{\lambda_{{ECW},{LT}} - \lambda_{{ECW},{AT}}}{\zeta_{LT} - \zeta_{AT}}},} & (30)\end{matrix}$

Eq. (7) can be solved with the help of Eqs. (9) and (27):

$\begin{matrix}{{ECW}_{EX} = \frac{{ECW} - {A \cdot {ICV}} + {\left( {{A \cdot \zeta_{AT}} - \lambda_{{ECW},{AT}}} \right) \cdot M}}{\left( {1 + {\left( {{A \cdot \zeta_{AT}} - \lambda_{{ECW},{AT}}} \right)D_{ECW}}} \right)}} & (31)\end{matrix}$

wherein D_(ECW) is the density of the extracellular water (=0.99823kg/litre). Once the mal-hydration volume ECW_(EX) has been determined(and thus the mal-hydration mass M_(EX)), the lean tissue mass M_(LT)can be calculated from Eq. (27) and the adipose tissue mass M_(AT) byEq. (13).

As can be seen from all five examples, the chemical or physicalproperties that have to be determined of the patient may vary from oneexample to another. It is yet in all examples possible to determine atleast one of a mal-hydration component, an adipose tissue component anda lean tissue component of the patient on the basis of the determinedchemical or physical properties and previously determined values of amass or volume fraction of water in lean tissue and a mass or volumefraction of water in adipose tissue. The general concept of the presentinvention is therefore not limited to specific methods where specificproperties of a patient have to be determined. The key element of theinvention to derive the at least one body component is to makeappropriate use of the previous determined values of a mass or volumefraction of water in lean tissue and a mass or volume fraction of waterin adipose tissue. The same applies not just to the method but also toany device according to the invention.

The method according to Example 1 is now used to describe an embodimentof a device according to the invention in detail (FIG. 3). The device 10comprises an evaluation unit that consists of a microprocessor unit 1which in turn comprises a microprocessor program storage unit 1 a. Bymeans of a communication link 4 the microprocessor unit 1 is connectedto an interface unit 2 and a computer storage unit 3. A program fordetermining the masses M_(EX), M_(LT) and/or M_(AT) of a patient isstored in the microprocessor program storage unit 1 a. This program mayhave been transferred beforehand to the microprocessor program storageunit 1 a from a computer program product like a floppy disk, a CD-ROM, aDVD, a memory stick, a server or any other suitable storage medium onwhich the program was stored. In this case the device 10 comprises thenecessary interface circuitry (not shown) whose design is—dependent ofthe type of computer program product—obvious to a person skilled in theart.

The microprocessor program controls the device to determine patientimpedance values for two or more frequencies. For the correspondingmeasurement the device 10 comprises a bioimpedance measurement means 5which is connected to the interface unit 2 by a communication link 6.The bioimpedance measurement means 5 can be capable of automaticallycompensating for influences on the impedance data like contactresistances. An example for such a bioimpedance measurement means 5 is adevice from Xitron Technologies distributed under the trademark Hydra™and also described in WO 92/19153.

For the bioimpedance measurement various electrode arrangements arepossible. In FIG. 3 only two electrode elements 5 a and 5 b are attachedto the bioimpedance measurement device 5. Each of the electrode units 5a and 5 b consists of a current injection electrode and a potentialpick-up electrode (not shown). By applying the two electrode units 5 aand 5 b to the wrist and the ankle of a patient, respectively, asoutlined in the left part of FIG. 4, the whole body impedance may bedetermined. Under this electrode configuration the body may be regardedas a combination of several homogenous cylinders, representing trunk,legs and arms. Average contributions of these components to the totalimpedance are also provided in FIG. 4, mainly resulting from thediffering cross-sections of the cylinders.

By using additional electrodes on shoulder and hip, these cylindricalsegments may be measured separately, thereby possibly increasing theaccuracy of volume determinations. Such a configuration is displayed onthe right hand side of FIG. 4. Additional electrode units 5 a′ and 5 b′are attached close to the shoulder and the hip of the patient enabling asegmental approach to the body elements leg, arm and trunk.

The program stored in the microprocessor storage unit 1 a initiates animpedance measurement at least two given frequencies and records thecorresponding current and voltage signals, both being below criticalthresholds so that the device just non-invasively probes the patientimpedance without having any impact on the patient at all. The devicecan easily be applied by the patient him- or herself without necessarilyrequiring medical staff.

Returning to the embodiment shown in FIG. 3, the weight or whole bodymass M of the patient can be entered into the device 10 via any inputunit (not explicitly shown) connected to or being part of the interfaceunit 2 (e.g. a keyboard, touch screen etc.). This may be assisted by aweighing means 7 linked to the interface unit 2 by a communication link8.

In the embodiment shown in FIG. 3 the interface unit 2 serves as aninterface by which the values of the whole body mass M and any measuredimpedance or applied current and voltage values are directly exchangedvia the communication link 4 between the computer storage unit 3, theprogram stored in the microprocessor program storage unit 1 a, theinterface 2 and the bioimpedance measurement means 5. As indicated it isalso possible that any data from or to the weighing means 7 are directlytransferred between the connected components via the communicationlinks.

The program stored in the microprocessor storage unit 1 a is now—withthe help of stored previously established data—processing the storeddata in order to determine any contributions of various body tissuescomponents to the whole body mass M.

As outlined above the ECW is determined by exploiting the fact that theelectrical impedance of body tissue changes when alternating currents ofdifferent frequencies are applied to the patient via the electrodes. Atlow frequencies the cell membranes behave as insulators and the appliedcurrent passes only through the ECV spaces, i.e. the ECW volume. At highfrequencies the cell membranes become more conductive and thus currentpasses through both the ICV and ECV spaces. Measurement of the impedanceover at least two frequencies, better over a range of frequencies,allows the determination of both the ECW and the ICW. In the prior artas described above such methods have been disclosed. A more refinedmodel was developed recently by the same inventors as of the presentinvention in the patent application PCT/EP2004/007023 whose disclosureis hereby explicitly enclosed in the current application by reference.

Once any values for the ECW, ICW and whole body mass M as chemical orphysical properties of the patient have been determined themicroprocessor program applies Eqs. (10) to (13) to receive values forat least one of a mal-hydration component, a adipose tissue componentand a lean tissue component, here the masses M_(EX), M_(LT) and M_(AT)of all three components, on the basis of previously determined values ofa mass or volume fraction of water in lean tissue and a mass or volumefraction of water in adipose tissue.

The results are finally completely or partially passed on to an outputunit 9 which typically is a display device which displays the results toa user. Further results—independent whether as an intermediate or as anadditional result—might add to the informative character of the display.

The compartmental results may be stored in the device to enable a trendanalysis including previously derived results. It has also proved usefulto smooth the data by deriving weighted average values from the latestand the previous data. For this purpose various algorithms are availablein the art to reduce statistical scatter in the data. A usefulimprovement in the averaging procedure for the current result to bedisplayed was obtained by giving the latest measurement the highestweight and by decreasing the weight of other, previous measurements withincreasing time that has passed since the measurements were taken.

The disclosed device and method according to the invention are henceable to provide for a powerful and more accurate technique for themanagement of the hydration status of a patient. In case the weightM_(AT) of the adipose tissue component and/or the weight M_(LT) of thelean tissue component are also determined the invention is yieldinguseful further results which allow conclusions about the nutritionand/or training status of the patient. This is not dependent on whetherthe patient is really mal-hydrated or not.

It is important to note that the concept of the invention is not limitedto the use of a bioimpedance measurement means on one hand and on theapplication of Example 1 on the other hand. For applying the concept ofExample 1 it is not relevant as to how the values of the properties ofthe patient have been determined. In particular Examples 2, 3 and 4provide examples of such variations of the concept of the invention.Instead of bioimpedance other techniques may be applied that aresuitable to reveal the separate character of the lean tissue on one handand the adipose tissue on the other hand. As example technique todetermine the lipid mass M_(LIPID) or the total bone mineral contentmass M_(TBMC) DXA measurements are recalled. Total body water, ICW orECW may also be derived by dilution methods.

In the simplest embodiment of a device according to the invention such adevice comprises an input unit by which such chemical or physicalproperty values may be entered into the device. As described above sucha device may also comprise at least partly the measurement means todetermine the chemical or physical properties of the patient. In such acase it is possible that the evaluation unit also controls themeasurement unit for carrying out the measurement of the chemical orphysical properties of the patient in an automated manner.

Hence management of any individual is possible, independent of anytreatment modality. The invention is particularly applicable forpatients which undergo end stage renal failure treatments likehemodialysis, hemofiltration, hemodiafiltration or any forms ofperitoneal dialysis (all these treatment modalities are summarisedthroughout this patent application by the terminology “a dialysistreatment”). A characterisation of hydration status might also be highlydesirable within the intensive care setting, since highly abnormalelectrolyte- and fluid conditions are frequent for such patients.Furthermore, measurement in virtually any setting where nutrition orfitness parameters are required, including home, pharmacies, medicalpractices, dialysis units, wards, fitness centres, etc., would bepractical.

1. A method to determine at least one of a mal-hydration component, anadipose tissue component and a lean tissue component of a patientcomprising the steps of: determining chemical or physical properties ofthe patient and deriving the at least one component on the basis of thedetermined chemical or physical properties and previously determinedvalues of a mass or volume fraction of water in lean tissue and a massor volume fraction of water in adipose tissue.
 2. The method accordingto claim 1 characterised in that the at least one component is the massof that component of the patient.
 3. The method according to claim 1characterised in that the at least one component is the volume of thatcomponent of the patient.
 4. The method according to claim 1characterised in that the chemical or physical properties of the patientcomprise at least one of the whole body mass, the lipid mass and thetotal bone mineral content mass of the patient.
 5. The method accordingto claim 1 characterised in that the chemical or physical properties ofthe patient comprise the volume or mass of at least one of the totalwater, the extracellular water and the intracellular water of thepatient.
 6. The method according to claim 1 characterised in that thepreviously determined values comprise the mass or volume fraction of thetotal water in lean tissue and the mass or volume fraction of the totalwater in adipose tissue.
 7. The method according to claim 1characterised in that the previously determined values comprise the massor volume fraction of extracellular water in lean tissue and the mass orvolume fraction of extracellular water in adipose tissue.
 8. The methodaccording to claim 1 characterised in that the previously determinedvalues comprise the mass or volume fraction of intracellular water inlean tissue and the mass or volume fraction of intracellular water inadipose tissue.
 9. A device for carrying out the method according toclaim 1 comprising: a measurement and/or input unit (5) configured toprovide values for the chemical or physical properties of the patient tobe determined, an evaluation unit (1) configured to derive the at leastone component on the basis of the determined properties of the patientand previously determined values of a mass or volume fraction of waterin lean tissue and a mass or volume fraction of water in adipose tissueand a communication link between the measurement and/or input unit andthe evaluation unit.
 10. The device according to claim 9 characterisedin that the evaluation unit is also configured to control themeasurement and/or input unit for determining at least one of thechemical or physical properties of the patient.
 11. The device accordingto claim 9 characterised in that the evaluation unit is a microprocessorunit which in turn comprises a microprocessor program storage unit,wherein in the microprocessor program storage unit a program forderiving the at least one component on the basis of the determinedchemical or physical properties of the patient and previously determinedvalues of a mass or volume fraction of water in lean tissue and a massor volume fraction of water in adipose tissue is stored.
 12. The deviceaccording to claim 11 characterised in that the program stored in themicroprocessor storage unit also controls the measurement and/or inputunit for determining at least one of the chemical or physical propertiesof the patient.
 13. The device according to claim 9 characterised inthat the measurement unit comprises a bioimpedance measurement means todetermine at least one of the chemical or physical properties of thepatient.
 14. The device according to claim 13 characterised in that theat least one of the chemical or physical properties of the patientcomprise at least one of the extracellular water volume, theintracellular water volume or the total body water volume of thepatient.
 15. The device according to claim 1 characterised in that themeasurement unit comprises scales to determine at least one of thechemical or physical properties of the patient.
 16. The device accordingto claim 15 characterised in that the at least one of the chemical orphysical properties is the whole body mass of the patient.
 17. Thedevice according to claim 9 characterised in that it further comprisesan output unit linked to the evaluation unit for outputting, preferablydisplaying, any data derived by the evaluation unit.
 18. A computerprogram product characterised in that it comprises a storage medium onwhich a microprocessor program to be stored in the microprocessorprogram storage unit of the device according to claim 11 is stored.